Notch-ing up knowledge on molecular mechanisms of skin fibrosis: focus on the multifaceted Notch signalling pathway

Journal of Biomedical Science

Alexander Nystrom¹  Eleonora Candi²  May El Hachem³  Giovanna Zambruno⁴  Angelo Giuseppe Condorelli⁴  Daniele Castiglia⁵ 

[1] Department of Dermatology, Medical Faculty, Medical Center, University of Freiburg, Freiburg, Germany;Department of Experimental Medicine, University of Rome “Tor Vergata”, via Montpellier, 1, 00133, Rome, Italy;IDI-IRCCS, via Monti di Creta 104, 00167, Rome, Italy;Dermatology Unit and Genodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children’s Hospital, IRCCS, Piazza Sant’ Onofrio 4, 00165, Rome, Italy;Genodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children’s Hospital, IRCCS, Piazza Sant’ Onofrio 4, 00165, Rome, Italy;Laboratory of Molecular and Cell Biology, IDI-IRCCS, via Monti di Creta 104, 00167, Rome, Italy;

关键词: Dermal fibroblasts;    Hypertrophic scar;    Keloid;    Systemic sclerosis;    Epidermolysis bullosa;    Transforming growth factor-β1;    Extracellular matrix;    JAG1;    NOTCH1;    Gamma-secretase inhibitor;   

DOI  :  10.1186/s12929-021-00732-8

来源: Springer

【 摘 要 】

Fibrosis can be defined as an excessive and deregulated deposition of extracellular matrix proteins, causing loss of physiological architecture and dysfunction of different tissues and organs. In the skin, fibrosis represents the hallmark of several acquired (e.g. systemic sclerosis and hypertrophic scars) and inherited (i.e. dystrophic epidermolysis bullosa) diseases. A complex series of interactions among a variety of cellular types and a wide range of molecular players drive the fibrogenic process, often in a context-dependent manner. However, the pathogenetic mechanisms leading to skin fibrosis are not completely elucidated. In this scenario, an increasing body of evidence has recently disclosed the involvement of Notch signalling cascade in fibrosis of the skin and other organs. Despite its apparent simplicity, Notch represents one of the most multifaceted, strictly regulated and intricate pathways with still unknown features both in health and disease conditions. Starting from the most recent advances in Notch activation and regulation, this review focuses on the pro-fibrotic function of Notch pathway in fibroproliferative skin disorders describing molecular networks, interplay with other pro-fibrotic molecules and pathways, including the transforming growth factor-β1, and therapeutic strategies under development.

【 授权许可】

CC BY